Metabolism / Metabolites
Butanediol is metabolized in the liver… β-hydroxybutyric acid (a major metabolite) is further metabolized to carbon dioxide in the tricarboxylic acid cycle, accounting for approximately 90% of the administered dose. In other studies… After feeding rats with 1,3-butanediol for 3 to 7 weeks, blood levels of β-hydroxybutyric acid were also found to be higher than normal. R- and S-1,3-butanediol showed similar absorption rates in isolated livers of fed or starved rats. R-1,3-butanediol was primarily converted to the physiological ketone bodies R-3-hydroxybutyric acid and acetoacetic acid. Only 29–38% of the S-enantiomer was converted to physiological ketone bodies. The S-enantiomer was further metabolized to S-3-hydroxybutyric acid (a non-natural compound), lipids, and carbon dioxide. Based on these results, it can be concluded that the tested substance is metabolized via physiological pathways, indicating a low potential for accumulation.

Toxicity Summary
Identification and Uses: 1,3-Butanediol is a colorless, odorless, viscous liquid with a sweet and bitter aftertaste. It is used as an intermediate in polyester plasticizers; a humectant in cellophane and tobacco; and as a substitute for glycerin in the cosmetics and pharmaceutical industries. 1,3-Butanediol also has some antifungal properties. Currently, it is not registered as a pesticide in the United States, but approved pesticide uses may change periodically, so it is necessary to consult federal, state, and local authorities for currently approved uses. Human Exposure and Toxicity: 1,3-Butanediol is non-irritating to human skin or mucous membranes. Contact with the eyes causes immediate and severe stinging, which is quickly and completely relieved by rinsing with water. Animal Studies: One case of eye irritation was reported in an animal, but the intensity of irritation appears to be lower in rabbits. Acute oral toxicity in rodents is low. After two years of feeding diets supplemented with 1%, 3%, or 10% 1,3-butanediol (approximately 643, 1960, or 6230 mg/kg body weight/day for males, and approximately 844, 2330, or 7300 mg/kg body weight/day for females), no treatment-related effects on mortality, weight gain, organ weight, hematological, histopathological, or tumor changes were observed. In feeding studies where 1,3-butanediol replaced carbohydrates as an energy source, effects on the central nervous system were found in rats, dogs, and calves. In lactating goats fed diets containing 1,3-butanediol, glucose levels were decreased and β-hydroxybutyrate levels were increased. 1,3-Butanediol exhibits fetal toxicity in pregnant rats, and a multigenerational rat feeding study suggested it may reduce male fertility. No genotoxicity (dominant lethality or chromosomal damage) was observed in rats administered orally.
Interactions
1,3-Butanediol and phlorizin have been used to induce ketosis and hypoglycemia in beef cattle. Oral administration of butylenediol increases blood concentrations of β-hydroxybutyrate (BHB) and plasma concentrations of non-esterified fatty acids (NEFA), and decreases serum glucose levels. Subcutaneous injection of phlorizin on top of oral butylenediol further increases NEFA and BHB concentrations and decreases glucose levels. Adding niacin to diets of beef cattle fed phlorizin and butylenediol leads to increased serum glucose concentrations and decreased blood concentrations of β-hydroxybutyrate (BHB) and plasma concentrations of non-esterified fatty acids (NEFA).
Previously reported evidence suggests that 1,3-butanediol (BD) can enhance the hepatotoxic effects of a single small dose of carbon tetrachloride (CCl4) in a dose-dependent manner. This study further clarifies the quantitative relationship between the severity of BD-induced ketosis and the observed enhancing effect, and highlights the importance of using ketone bodies (KB) to predict the potential harm of BD-CCl4 interactions. Liver injury in male Sprague-Dawley rats was modulated by altering the concentration of BD solution ingested prior to CCl4 challenge (0.1 ml/kg, intraperitoneal injection). These data were compared with ketone body levels in plasma, liver tissue, and urine. Dose-dependent metabolic ketosis was observed for 7 consecutive days within a dose range of 1.1 to 9.9 g/kg/day with BD. Plasma and liver data showed good correlation. Furthermore, the enhancing effect of BD on CCl4-induced liver injury was dose-dependent within the same dose range; the minimum effective dose for BD enhancement was estimated to be 1.1 g/kg/day. A highly significant linear correlation was found between liver or plasma ketone body (KB) levels and liver function indicators (ALT, OCT). A semi-quantitative method also revealed a correlation between urinary KB levels and liver function indicators. These results suggest that plasma KB concentration may help predict the enhancing effect of BD on CCl4-induced liver necrosis. Over 28 days, four steers were administered 1,3-butanediol, which can cause ketoacidosis, and phlorizin, which can cause glycosuria. The cattle were also fasted for 9 days. The effects of different treatments on blood and liver metabolite concentrations and glucose metabolism kinetics were determined. Treatment groups included a control group, a control group (diet supplemented with 1,3-butanediol and injected with phlorizin), and a fasting group. Fasting led to hypoinsulinemia and a 60% decrease in liver glycogen content. The 1,3-butanediol plus phlorizin group and fasting resulted in a 18% and 19% decrease in plasma glucose concentration, respectively, and a 2.5-fold and 6-fold increase in plasma free fatty acid concentration, respectively. The average irreversible glucose loss in the control group, the 1,3-butanediol plus phlorizin group, and the fasting group were 371 g/day, 541 g/day, and 182 g/day, respectively. The addition of phlorizin to 1,3-butanediol increased liver ketone body concentrations, causing glycosuria, ketoacidosis, and ketoacidosis, but had no effect on plasma insulin, glucagon, or growth hormone concentrations, or on liver triglyceride and glycogen content. Cattle treated with butane plus phlorizin did not exhibit all common symptoms of prolactinemia, but this therapy still provides a basis for studying the etiology and effects of ketosis. Rats given 1,3-butanediol showed enhanced cholestatic responses to taurocholic acid or manganese bilirubin injections; injection of α-naphthyl isothiocyanate enhanced hyperbilirubinemia, but did not enhance bile flow inhibition. Non-human toxicity values: Oral LD50 in rats: 22800 mg/kg. Subcutaneous LD50 in mice: 16.5 mL/kg. Subcutaneous LD50 in rats: 20.1 mL/kg. Oral LD50 in guinea pigs: 11 g/kg. For more complete non-human toxicity data on 1,3-butanediol (6 out of 6), please visit the HSDB record page.

[1]. Protective action of 1,3-butanediol in cerebral ischemia. A neurologic, histologic, and metabolic study. J Cereb Blood Flow Metab. 1987 Dec;7(6):794-800.

[2]. Nutritional and metabolic studies in humans with 1,3-butanediol. Fed Proc. 1975 Nov;34(12):2171-6.

1,3-Butanediol is a butanediol compound containing two hydroxyl groups at the 1 and 3 positions. It is both butanediol and a diol. 1,3-Butanediol is found in pepper (C. annuum). 1,3-Butanediol is an organic compound belonging to the alcohol class. It is commonly used as a solvent in food flavorings and is also a comonomer of some polyurethane and polyester resins. It is one of the four stable isomers of butanediol. In biology, 1,3-Butanediol is used as a hypoglycemic agent. 1,3-Butanediol belongs to the secondary alcohol class. Secondary alcohols contain a secondary alcohol functional group, with the general formula HOC(R)(R') (R,R' = alkyl, aryl). See also: Avobenzone; Butanediol (ingredient)... See more...

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Therapeutic Uses
/Experimental Treatment/ This study investigated the effects of 1,3-Butanediol on the selective loss of CA1 pyramidal neurons following transient near-complete forebrain ischemia. Injections of 55 mmol/kg body weight of 1,3-butanediol at 24 and 36 hours after cerebral ischemia 10 minutes prior significantly reduced CA1 neuronal damage 72 hours later compared to the saline treatment group. Similar treatment with ethanol did not produce a significant protective effect. 1,3-butanediol treatment also failed to reduce neuronal loss when ischemia time was prolonged to 15 minutes, or when a single dose was administered at 24 or 36 hours after 10 minutes of ischemia. However, a single dose 5 minutes after reversal of 10 minutes of ischemia effectively reduced cell loss. The difference in efficacy of 1,3-butanediol at 10 and 15 minutes of ischemia is consistent with many previous studies, indicating that the processes leading to CA1 neuronal loss are altered with prolonged ischemia time. Previous studies have found that 1,3-butanediol can reduce damage to other ischemic neuronal subsets but has no effect on CA1 neurons, which likely reflects the longer ischemia time used in previous studies. This study demonstrates that administration of 1,3-butanediol following transient ischemic attack is a novel approach to intervene in CA1 neuronal loss after ischemia, effective even when administration is initiated after prolonged reperfusion.
/Experimental Treatment/ The biochemical effects of S-1,3-butanediol on streptozotocin-induced diabetic rats were investigated. Rats were induced to develop diabetes by intraperitoneal injection of 40 mg/kg body weight streptozotocin (dissolved in sodium citrate buffer). Treatment was then administered intraperitoneally with 25 mmol/kg body weight S-1,3-butanediol. Streptozotocin-induced diabetic rats exhibited significantly elevated blood glucose levels, as well as significantly elevated levels of cholesterol, triglycerides, and free fatty acids. Liver and kidney glycogen levels were significantly reduced in diabetic rats. Butanediol treatment restored blood glucose and glycogen levels to normal, but had no significant effect on protein and lipid levels.
/Experimental Treatment/ We have previously demonstrated that intrastriatal injection of aminooxyacetic acid (AOAA) can cause striatal damage through a secondary excitotoxic mechanism associated with impaired oxidative phosphorylation. In this study, we found that the specific complex I inhibitor rotenone produced neurochemical changes in the striatum similar to those of AOAA, consistent with the effects of AOAA on energy metabolism. MK-801 dose-dependently blocked AOAA-induced damage, completely protecting the striatum from GABA and substance P depletion at a dose of 3 mg/kg. Pretreatment with 1,3-butanediol or coenzyme Q10 (both compounds believed to improve energy metabolism) significantly reduced AOAA-induced damage. These results further confirm that AOAA causes striatal excitotoxic damage as a result of energy depletion and suggest potentially useful therapeutic strategies for neurodegenerative diseases. /Experimental Treatment/ To evaluate the therapeutic value of 1,3-butanediol in ethylene glycol poisoning, we orally administered 6 mL/kg body weight of commercially available antifreeze (0 hours) to mixed-breed dogs, followed by intravenous injections of 5.5 mL/kg body weight of 1,3-butanediol solution (20% saline) every 6 hours, starting at 8, 12, and 21 hours, for a total of 7 times. Serum glycolic acid concentration was quantified using high-performance liquid chromatography (HPLC). Three dogs treated with ethylene glycol only but not 1,3-butanediol died due to elevated serum glycolic acid levels. Five dogs were treated with both ethylene glycol and 1,3-butanediol. Of the two dogs treated at 8 hours, one survived and one died at 39 hours; one dog treated at 12 hours and one dog treated at 21 hours both survived; one dog died shortly after treatment began at 21 hours (27 hours). Four out of the five dogs showed a significant decrease in serum glycolic acid concentration after 1,3-butanediol treatment, indicating its effective inhibition of alcohol dehydrogenase-dependent glycolic acid production.
/Experimental Treatment/ Studies have shown that prepartum feeding of sows with 1,3-butanediol can improve the metabolic status and survival rate of newborn piglets. This study aimed to evaluate the effects of short-term, prepartum feeding of low concentrations of 1,3-butanediol on the reproductive performance of pigs and sows. A secondary objective was to determine whether pre-farrowing 1,3-butanediol (1,3-butanediol) feeding affected the survival and weight gain of low-birth-weight piglets, sow body weight, and subsequent sow reproductive performance. In a large commercial farm, 2537 sows were fed either a pre-farrowing diet (0% or 4.55% 1,3-butanediol) on day 108±3 of gestation. 1,3-Butanediol provided 8% of the total metabolizable energy. Litter weight was equalized by cross-feeding sows fed the same pre-farrowing diet. Piglets were weaned at 16±3 days postpartum, and sow estrus recovery and conception rates were measured. Pre-farrowing 1,3-butanediol feeding significantly reduced pre-weaning piglet mortality (P=0.01), from 1.44 to 1.24 piglets per litter. This reduction in piglet mortality was independent of the duration of 1,3-butanediol feeding (4 to 11 days). In a study of 750 litters of piglets, four piglets with lower birth weights from each litter were randomly selected, marked, and monitored to determine the effects of 1,3-butanediol on the survival rate and pre-weaning weight gain of piglets with the highest mortality risk. The results showed that 1,3-butanediol significantly reduced pre-weaning mortality in these low birth weight piglets by 5.27% (P=0.01). Based on these data, short-term prepartum feeding with 1,3-butanediol can effectively improve the pre-weaning performance of piglets, and the required concentration is lower than previously reported.

C4H10O2

90.12

90.068

107-88-0

(R)-(-)-1,3-Butanediol;6290-03-5

7896

Viscous liquid
Pure compound is colorless

1.0±0.1 g/cm3

207.0±0.0 °C at 760 mmHg

-54ºC

121.1±0.0 °C

0.1±0.8 mmHg at 25°C

1.438

-0.69

2

2

2

6

28.7

0

O([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])O[H]

PUPZLCDOIYMWBV-UHFFFAOYSA-N

InChI=1S/C4H10O2/c1-4(6)2-3-5/h4-6H,2-3H2,1H3

butane-1,3-diol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: ≥ 500 mg/mL (5548.16 mM)
DMSO: 100 mg/mL (1109.63 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (27.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (27.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: ≥ 1.72 mg/mL (19.09 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 17.2 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)